This proposal is a request for funds from the Fogarty International Center to study the histidine kinases [HK] of Candida albicans and Aspergillus fumigatus The collaborative efforts of Dr R Calderone [Georgetown University] and Dr Ruoyu Li [Peking University First Hospital, Beijing, China] are to be utilized to understand the role of HK genes in the pathogenesis of candidiasis and aspergillosis. Dr Calderone is currently funded by the NIH-NIAID to characterize a specific HK from C albicans, while Dr. Li studies host immunity and the pathogenesis of aspergillosis Thus, the proposal combines the efforts of differently focused laboratories The project has four specific aims In aim 1, the temporal expression of HK genes from both organisms will be studied in animal models of each disease. Along with this objective, cytokine production in infected animals will be followed to assess the contribution of specific host responses to wild type and gene-deleted mutants Specific aim 2 will shift in emphasis to in vitro conditions, and the interaction ofA fumigatus and the corresponding gene-deleted strains with human neutrophils will be studied. In specific aim 3, clinical specimens from patients with oral or vaginal candidiasis infections as well as those with allergic or invasive aspergillosis will be screened by RT-PCR for HK gene transcription. In aim 4, the Calderone laboratory will complete the isolation of an A fumigatus HK gene originally found by the Li laboratory and construct gene-deleted strains for functional studies. In summary, the Li laboratory will provide expertise in the studies of immunity while the Calderone laboratory will assist the Li laboratory in molecular biology. Synergy will occur during this collaboration since the role of the HK in host responses will be defined while we will also further expand our understanding of the functions of HK genes from these organisms As expected, this collaboration will also provide new directions for the NIH parent grant of Dr Calderone [unreadable] [unreadable] [unreadable]